The purpose of the Rural Comorbidity and HIV consequences of Opioid use Research and Treatment Initiative (Rural Cohort) Coordinating Center (CC) is to coordinate and support a cohort collaboration of NIH funded studies as they conduct assessments and implement evidence-based practices to address opioid use, HIV and related comorbidities in their rural communities. The overarching purpose is to improve the overall health and outcomes of this vulnerable population. There is also an opportunity to increase the use of HIV prevention and care services and address opioid use in ways that are likely to reduce HIV incidence and prevent new HIV epidemics among substance users. Achieving these objectives will require a CC experienced in data harmonization, multi-site coordination, and research on substance use interventions and impact among substance using populations with and without HIV to comprehensively integrate clinical research data from multiple studies. The resulting large resource of comprehensively integrated clinical data from multiple studies will give researchers the potential to address important scientific and public health questions related to substance use and HIV prevention and outcomes among persons who inject drugs (PWID) that would not be possible with smaller studies. As the Rural Cohort CC, we will work with sites to allow complex, careful, and complete analysis of outcomes and results over many diverse populations using harmonized data from across sites. This will improve the statistical power to identify areas or sub-groups for research focus and to understand what interventions are proving successful in the broader context of the whole population of rural PWID (as opposed to in the target population of a single member site). Careful data harmonization will be paired with intuitive delivery tools to ensure that this high-quality data is made widely available to the member sites. The Rural Cohort CC team brings vast experience with data linkage and harmonization, methods development, statistical support for observational research, platform and tool development such as for the efficient and accurate collection of patient reported outcomes and outcomes adjudication, providing overall coordination for large collaborations of cohorts and studies, and a strong background in clinical epidemiology of HIV and substance use. This will allow us to assist the studies to improve and enhance data collection where appropriate, merge and harmonize data when feasible, and work together more closely to address the key questions on substance use, HIV, and outcomes in rural settings that cannot be addressed by individual studies.